Contractile responses to endothelin-1 are regulated by PKC phosphorylation of cardiac myosin binding protein-C in rat ventricular myocytes.

Journal of Molecular and Cellular Cardiology
Ioannis SmyrniasH Llewelyn Roderick

Abstract

The shortening of sarcomeres that co-ordinates the pump function of the heart is stimulated by electrically-mediated increases in [Ca2+]. This process of excitation-contraction coupling (ECC) is subject to modulation by neurohormonal mediators that tune the output of the heart to meet the needs of the organism. Endothelin-1 (ET-1) is a potent modulator of cardiac function with effects on contraction amplitude, chronotropy and automaticity. The actions of ET-1 are evident during normal adaptive physiological responses and increased under pathophysiological conditions, such as following myocardial infarction and during heart failure, where ET-1 levels are elevated. In myocytes, ET-1 acts through ETA- or ETB-G protein-coupled receptors (GPCRs). Although well studied in atrial myocytes, the influence and mechanisms of action of ET-1 upon ECC in ventricular myocytes are not fully resolved. We show in rat ventricular myocytes that ET-1 elicits a biphasic effect on fractional shortening (initial transient negative and sustained positive inotropy) and increases the peak amplitude of systolic Ca2+ transients in adult rat ventricular myocytes. The negative inotropic phase was ETB receptor-dependent, whereas the positive inotropic respons...Continue Reading

Citations

Feb 1, 2019·Journal of Cellular and Molecular Medicine·Leilei YinXinhua Yin
Oct 16, 2018·Cardiovascular Research·Elisabeth KaiserPeter Lipp
Jul 17, 2019·Cold Spring Harbor Perspectives in Biology·Guillaume GilbertH Llewelyn Roderick
Apr 13, 2019·Annual Review of Genomics and Human Genetics·Raquel YottiJonathan G Seidman
May 31, 2019·Proceedings of the National Academy of Sciences of the United States of America·James W McNamaraSakthivel Sadayappan
Feb 25, 2021·Archives of Biochemistry and Biophysics·Alexander V MaltsevYury M Kokoz

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